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- PDB-8oz0: Structure of a human 48S translation initiation complex with eIF4... -
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Basic information
Entry | Database: PDB / ID: 8oz0 | ||||||||||||
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Title | Structure of a human 48S translation initiation complex with eIF4F and eIF4A | ||||||||||||
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![]() | TRANSLATION / eIF4A / eIF4F / initiation / ribosome / mRNA | ||||||||||||
Function / homology | ![]() positive regulation of eukaryotic translation initiation factor 4F complex assembly / : / male germ cell proliferation / eukaryotic initiation factor eIF2 binding / positive regulation of mRNA binding / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / positive regulation of translation in response to endoplasmic reticulum stress / HRI-mediated signaling ...positive regulation of eukaryotic translation initiation factor 4F complex assembly / : / male germ cell proliferation / eukaryotic initiation factor eIF2 binding / positive regulation of mRNA binding / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / positive regulation of translation in response to endoplasmic reticulum stress / HRI-mediated signaling / response to kainic acid / macromolecule biosynthetic process / viral translational termination-reinitiation / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / eukaryotic translation initiation factor 3 complex, eIF3e / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / cap-dependent translational initiation / negative regulation of translational initiation in response to stress / PERK-mediated unfolded protein response / methionyl-initiator methionine tRNA binding / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / eukaryotic translation initiation factor 3 complex, eIF3m / eukaryotic initiation factor 4E binding / PERK regulates gene expression / regulation of cellular response to stress / IRES-dependent viral translational initiation / translation reinitiation / eukaryotic translation initiation factor 2 complex / eukaryotic translation initiation factor 3 complex / nuclear stress granule / RNA cap binding / eukaryotic translation initiation factor 4F complex / formation of cytoplasmic translation initiation complex / cytoplasmic translational initiation / multi-eIF complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / regulation of translational initiation in response to stress / translation factor activity, RNA binding / eukaryotic 43S preinitiation complex / mRNA cap binding / formation of translation preinitiation complex / Deadenylation of mRNA / miRNA-mediated gene silencing by inhibition of translation / negative regulation of peptidyl-threonine phosphorylation / eukaryotic 48S preinitiation complex / M-decay: degradation of maternal mRNAs by maternally stored factors / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of peptidyl-serine phosphorylation / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / TNFR1-mediated ceramide production / protein-synthesizing GTPase / negative regulation of DNA repair / negative regulation of RNA splicing / metal-dependent deubiquitinase activity / mammalian oogenesis stage / regulation of translational initiation / positive regulation of protein localization to cell periphery / supercoiled DNA binding / activation-induced cell death of T cells / neural crest cell differentiation / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / NF-kappaB complex / oxidized purine DNA binding / GDP-dissociation inhibitor activity / cysteine-type endopeptidase activator activity involved in apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / translation at presynapse / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of phagocytosis / erythrocyte homeostasis / rRNA modification in the nucleus and cytosol / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / pigmentation / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
![]() | Brito Querido, J. / Sokabe, M. / Diaz-Lopez, I. / Gordiyenko, Y. / Fraser, C.S. / Ramakrishnan, V. | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: The structure of a human translation initiation complex reveals two independent roles for the helicase eIF4A. Authors: Jailson Brito Querido / Masaaki Sokabe / Irene Díaz-López / Yuliya Gordiyenko / Christopher S Fraser / V Ramakrishnan / ![]() ![]() Abstract: Eukaryotic translation initiation involves recruitment of the 43S pre-initiation complex to the 5' end of mRNA by the cap-binding complex eIF4F, forming the 48S translation initiation complex (48S), ...Eukaryotic translation initiation involves recruitment of the 43S pre-initiation complex to the 5' end of mRNA by the cap-binding complex eIF4F, forming the 48S translation initiation complex (48S), which then scans along the mRNA until the start codon is recognized. We have previously shown that eIF4F binds near the mRNA exit channel of the 43S, leaving open the question of how mRNA secondary structure is removed as it enters the mRNA channel on the other side of the 40S subunit. Here we report the structure of a human 48S that shows that, in addition to the eIF4A that is part of eIF4F, there is a second eIF4A helicase bound at the mRNA entry site, which could unwind RNA secondary structures as they enter the 48S. The structure also reveals conserved interactions between eIF4F and the 43S, probaby explaining how eIF4F can promote mRNA recruitment in all eukaryotes. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 2.8 MB | Display | ![]() |
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-Validation report
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-Related structure data
Related structure data | ![]() 17297MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Eukaryotic translation initiation factor ... , 18 types, 18 molecules 5678ABCDEFGHIJKUx2
#1: Protein | Mass: 52281.633 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Eukaryotic translation initiation factor 3 subunit E Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 37593.645 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit F Source: (natural) ![]() |
#3: Protein | Mass: 35662.016 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit G Source: (natural) ![]() |
#4: Protein | Mass: 39979.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit H Source: (natural) ![]() |
#6: Protein | Mass: 166903.781 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit A Source: (natural) ![]() |
#7: Protein | Mass: 25083.619 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit K Source: (natural) ![]() |
#8: Protein | Mass: 42555.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit M Source: (natural) ![]() |
#9: Protein | Mass: 36161.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 2 subunit 1 Source: (natural) ![]() |
#10: Protein | Mass: 51178.406 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 2 subunit 3 Source: (natural) ![]() |
#11: Protein | Mass: 36543.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit I Source: (natural) ![]() |
#12: Protein | Mass: 16488.449 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Eukaryotic translation initiation factor 1A / Source: (gene. exp.) ![]() ![]() ![]() |
#13: Protein | Mass: 49301.750 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Eukaryotic translation initiation factor 5 / Source: (gene. exp.) ![]() ![]() ![]() |
#14: Protein | Mass: 92593.414 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit B Source: (natural) ![]() |
#15: Protein | Mass: 105503.945 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit C Source: (natural) ![]() |
#16: Protein | Mass: 66803.734 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit L Source: (natural) ![]() |
#26: Protein | Mass: 38454.484 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 2 subunit 2 Source: (natural) ![]() |
#52: Protein | Mass: 64060.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit D Source: (natural) ![]() |
#56: Protein | Mass: 155130.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Eukaryotic translation initiation factor 4 gamma / Source: (gene. exp.) ![]() ![]() |
-Protein/peptide , 1 types, 1 molecules 9
#5: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: 60S ribosomal protein L41 / Source: (natural) ![]() |
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+40S ribosomal protein ... , 30 types, 30 molecules LMNOPQRSTVXYZabcdefghijlmoqsvw
-RNA chain , 3 types, 3 molecules Wyz
#28: RNA chain | Mass: 555083.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: 18S rRNA / Source: (natural) ![]() |
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#53: RNA chain | Mass: 24231.510 Da / Num. of mol.: 1 / Source method: obtained synthetically / Details: Human initiator Met-tRNA-i / Source: (synth.) ![]() |
#54: RNA chain | Mass: 67626.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Details: mRNA / Source: (synth.) ![]() |
-Protein , 4 types, 5 molecules knp31
#42: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: Receptor of activated protein C kinase 1 / Source: (natural) ![]() |
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#45: Protein | Mass: 17630.598 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: Small ribosomal subunit protein uS13 / Source: (natural) ![]() |
#47: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: Small ribosomal subunit protein eS31 / Source: (natural) ![]() |
#55: Protein | Mass: 46207.824 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: Eukaryotic initiation factor 4A-I / Source: (gene. exp.) ![]() ![]() ![]() |
-Non-polymers , 2 types, 91 molecules 


#57: Chemical | #58: Chemical | ChemComp-MG / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Human 48S translation initiation complex / Type: COMPLEX / Entity ID: #1-#56 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid type: UltrAuFoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: OTHER / Nominal defocus max: 3000 nm / Nominal defocus min: 1200 nm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 47.88 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 241389 / Symmetry type: POINT | ||||||||||||||||||||||||
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